The present study aimed to verify the effect of bilateral intra-hippocampus administration of the... more The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; 3alpha, 5alpha-THP) in the forced swimming test (FST) and in the alpha4 and gamma2 GABA(A) receptor subunits gene expression. Results showed that bilateral intra-hippocampal allopregnanolone administration of 2.5 microg/rat ( P<0.05) reduced immobile behavior and increased climbing behavior in the FST. Overall, for all doses of allopregnanolone tested (1.25, 2.5, 5.0 microg/rat), an increase of gamma2 (P<0.05) GABA(A) subunit mRNA was observed. There was a higher increase in the gamma2 gene expression in the right hemisphere than in the left hemisphere (P<0.01) after allopregnanolone treatment. Intra-hippocampal allopregnanolone did not change the expression of the alpha4 subunits. In conclusion, intra-hippocampal administration of allopregnanolone produces an antidepressant-like effect in the FST at an intermediate dose, confirming the potential of neurosteroids as a new class of antidepressant drugs. Our findings suggest that the gamma2, but not the alpha4 GABA(A) subunit, needs further evaluation to be involved in the antidepressant effect of allopregnanolone in the hippocampus and that there is a hemispheric diversity in the biochemical effect of the drug.
Attention-deficit/hyperactivity disorder is related to altered functions in the dopaminergic and ... more Attention-deficit/hyperactivity disorder is related to altered functions in the dopaminergic and GABAergic pathways of cortical and subcortical brain areas The hyperactivity of attention-deficit/hyperactivity disorder is commonly modelled in rats after neonatal lesion with 6-hydroxydopamine (6-OHDA), and amphetamines are effective in reducing hyperactivity in this animal model. Our objectives were to evaluate whether cocaine reverses the motor hyperactivity of 6-OHDA-lesioned rats and to verify cocaine effects in altered mRNA expression of alpha2, alpha4, beta1 and beta2-GABAA subunits and GAD isoenzymes in the prefrontal cortex, hippocampus and striatum of 6-OHDA-lesioned rats. On PND4, 6-OHDA-lesioned or sham rats received 6-OHDA (100 microg intracisternal) or vehicle. Cocaine solution (0.1 mg/ml/day) was offered when adult for 23 days, using the two-bottle choice procedure. The subjects were evaluated in an open-field on the last day of cocaine treatment. 6-OHDA-lesioned rats showed increased locomotion and this hyperactivity was reversed during cocaine self-administration. 6-OHDA lesion caused an increase in the mRNA expression of GABAA subunits in specific brain areas and GAD isoenzymes in the hippocampus and striatum. Increased GAD65 and decreased GAD67 mRNA expression were also shown in the prefrontal cortex. Cocaine self-administration attenuated the effects of 6-OHDA lesions on the mRNA expression of alpha2-GABAA and beta2-GABAA subunits in the prefrontal cortex, reversed the mRNA expression of alpha2-GABAA subunits in the striatum and of alpha4-GABAA subunits in the prefrontal cortex and in the hippocampus, and reversed the mRNA expression of GAD65 and GAD67 in the brain areas studied. Our findings suggest that cocaine reverses some mRNA changes of GABAA subunits and GAD isoenzymes in reward circuits and the behavioural hyperactivity caused by 6-OHDA lesion.
The present study aimed to verify the effect of bilateral intra-hippocampus administration of the... more The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; 3alpha, 5alpha-THP) in the forced swimming test (FST) and in the alpha4 and gamma2 GABA(A) receptor subunits gene expression. Results showed that bilateral intra-hippocampal allopregnanolone administration of 2.5 microg/rat ( P<0.05) reduced immobile behavior and increased climbing behavior in the FST. Overall, for all doses of allopregnanolone tested (1.25, 2.5, 5.0 microg/rat), an increase of gamma2 (P<0.05) GABA(A) subunit mRNA was observed. There was a higher increase in the gamma2 gene expression in the right hemisphere than in the left hemisphere (P<0.01) after allopregnanolone treatment. Intra-hippocampal allopregnanolone did not change the expression of the alpha4 subunits. In conclusion, intra-hippocampal administration of allopregnanolone produces an antidepressant-like effect in the FST at an intermediate dose, confirming the potential of neurosteroids as a new class of antidepressant drugs. Our findings suggest that the gamma2, but not the alpha4 GABA(A) subunit, needs further evaluation to be involved in the antidepressant effect of allopregnanolone in the hippocampus and that there is a hemispheric diversity in the biochemical effect of the drug.
Attention-deficit/hyperactivity disorder is related to altered functions in the dopaminergic and ... more Attention-deficit/hyperactivity disorder is related to altered functions in the dopaminergic and GABAergic pathways of cortical and subcortical brain areas The hyperactivity of attention-deficit/hyperactivity disorder is commonly modelled in rats after neonatal lesion with 6-hydroxydopamine (6-OHDA), and amphetamines are effective in reducing hyperactivity in this animal model. Our objectives were to evaluate whether cocaine reverses the motor hyperactivity of 6-OHDA-lesioned rats and to verify cocaine effects in altered mRNA expression of alpha2, alpha4, beta1 and beta2-GABAA subunits and GAD isoenzymes in the prefrontal cortex, hippocampus and striatum of 6-OHDA-lesioned rats. On PND4, 6-OHDA-lesioned or sham rats received 6-OHDA (100 microg intracisternal) or vehicle. Cocaine solution (0.1 mg/ml/day) was offered when adult for 23 days, using the two-bottle choice procedure. The subjects were evaluated in an open-field on the last day of cocaine treatment. 6-OHDA-lesioned rats showed increased locomotion and this hyperactivity was reversed during cocaine self-administration. 6-OHDA lesion caused an increase in the mRNA expression of GABAA subunits in specific brain areas and GAD isoenzymes in the hippocampus and striatum. Increased GAD65 and decreased GAD67 mRNA expression were also shown in the prefrontal cortex. Cocaine self-administration attenuated the effects of 6-OHDA lesions on the mRNA expression of alpha2-GABAA and beta2-GABAA subunits in the prefrontal cortex, reversed the mRNA expression of alpha2-GABAA subunits in the striatum and of alpha4-GABAA subunits in the prefrontal cortex and in the hippocampus, and reversed the mRNA expression of GAD65 and GAD67 in the brain areas studied. Our findings suggest that cocaine reverses some mRNA changes of GABAA subunits and GAD isoenzymes in reward circuits and the behavioural hyperactivity caused by 6-OHDA lesion.
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